Lancing Drug Reservoirs into Subcutaneous Fat to Combat Obesity and Associated Metabolic Diseases.

Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self-administrable and minimally invasive transdermal drug delivery strategy for home-based long-term treatment of obesity and other diseases is developed. Specifically, ultrathin, core-shelled, and lance-shaped polymeric drug reservoirs (micro-lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet-induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core-shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity.

Colorimetric microneedle patches for multiplexed transdermal detection of metabolites.

Skin Interstitial Fluid (ISF) is an alternative source for biomarkers. Herein, a highly swellable microneedle patch (MNP) to rapidly extract ISF painlessly and bloodlessly is presented. The MNP is made of crosslinked methacrylated hyaluronic acid (MeHA) and dissolvable hyaluronic acid (HA) with the optimal balance of mechanical strength (0.6 N/MN) and absorption capability (16.22 µL in 20 min). Incorporated with wax-patterned and sensing-reagent-decorated test paper (TP) for multiplexed colorimetric detection of metabolites (glucose, lactate, cholesterol, and pH), this TP-MNP biosensor gives rapid color change in biomarker concentration-dependent manner based on specific enzymatic reactions, whereby allowing diagnosis by the naked eye or quantitative RGB analysis. Both the in vitro and in vivo experiments demonstrate the feasibility of TP-MNPs to detect multiple biomarkers in skin interstitial fluid within minutes. Such convenient and self-administrable profiling of metabolites shall be instrumental for home-based long-term monitoring and management of metabolic diseases.

Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery.

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases.